14-55138056-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002306.4(LGALS3):c.30G>A(p.Ala10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,500,236 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (10 hom.)
• Consequence: LGALS3 NM_002306.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.436

Genes affected

LGALS3 (HGNC:6563): (galectin 3) This gene encodes a member of the galectin family of carbohydrate binding proteins. Members of this protein family have an affinity for beta-galactosides. The encoded protein is characterized by an N-terminal proline-rich tandem repeat domain and a single C-terminal carbohydrate recognition domain. This protein can self-associate through the N-terminal domain allowing it to bind to multivalent saccharide ligands. This protein localizes to the extracellular matrix, the cytoplasm and the nucleus. This protein plays a role in numerous cellular functions including apoptosis, innate immunity, cell adhesion and T-cell regulation. The protein exhibits antimicrobial activity against bacteria and fungi. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 14-55138056-G-A is Benign according to our data. Variant chr14-55138056-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 712322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.436 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS3	NM_002306.4	c.30G>A	p.Ala10=	synonymous_variant	3/6	ENST00000254301.14
LGALS3	NM_001357678.2	c.72G>A	p.Ala24=	synonymous_variant	4/7
LGALS3	NR_003225.2	n.1074G>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS3	ENST00000254301.14	c.30G>A	p.Ala10=	synonymous_variant	3/6	1	NM_002306.4	P1

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 262 AN: 152114 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00306

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00169 AC: 293 AN: 173716 Hom.: 1 AF XY: 0.00171 AC XY: 157 AN XY: 92076

Gnomad AFR exome AF: 0.000830

Gnomad AMR exome AF: 0.000869

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000841

Gnomad FIN exome AF: 0.000237

Gnomad NFE exome AF: 0.00260

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00343 AC: 4622 AN: 1348004 Hom.: 10 Cov.: 31 AF XY: 0.00327 AC XY: 2148 AN XY: 657716

Gnomad4 AFR exome AF: 0.000534

Gnomad4 AMR exome AF: 0.000980

Gnomad4 ASJ exome AF: 0.00321

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.000302

Gnomad4 NFE exome AF: 0.00404

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome AF: 0.00172 AC: 262 AN: 152232 Hom.: 2 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74422

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00306

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00233 Hom.: 1

Bravo AF: 0.00205

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	LGALS3: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jul 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	5.2
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11538648; hg19: chr14-55604774; COSMIC: COSV54305113;